Triazolo Based-Thiadiazole Derivatives. Synthesis, Biological Evaluation and Molecular Docking Studies
2021
Аутори:
Kamoutsis, CharalamposFesatidou, Maria
Petrou, Anthi
Geronikaki, Athina
Poroikov, Vladimir
Ivanov, Marija
Soković, Marina
Ćirić, Ana
Carazo, Alejandro
Mladenka, Premysl
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
The goal of this research is to investigate the antimicrobial activity of nineteen previously
synthesized 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives. The compounds were
tested against a panel of three Gram-positive and three Gram-negative bacteria, three resistant strains,
and six fungi. Minimal inhibitory, bactericidal, and fungicidal concentrations were determined by a
microdilution method. All of the compounds showed antibacterial activity that was more potent
than both reference drugs, ampicillin and streptomycin, against all bacteria tested. Similarly, they
were also more active against resistant bacterial strains. The antifungal activity of the compounds
was up to 80-fold higher than ketoconazole and from 3 to 40 times higher than bifonazole, both of
which were used as reference drugs. The most active compounds (2, 3, 6, 7, and 19) were tested for
their inhibition of P. aeruginosa biofilm formation. Among them, compound 3 showed significantly
higher antibiofilm activity and appeared to be equipotent with ampicillin. The prediction of the
probable mechanism by docking on antibacterial targets revealed that E. coli MurB is the most suitable
enzyme, while docking studies on antifungal targets indicated a probable involvement of CYP51 in
the mechanism of antifungal activity. Finally, the toxicity testing in human cells confirmed their low
toxicity both in cancerous cell line MCF7 and non-cancerous cell line HK-2.
Кључне речи:
thiadiazole derivatives; triazole; antimicrobial; antifungal; biofilm; docking; toxicityИзвор:
Antibiotics, 2021, 10, 7, 804-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- EFSA-CDN project (ERDF)
DOI: 10.3390/antibiotics10070804
ISSN: 2079-6382
PubMed: 34356726